chr13-30463308-T-C

Variant names:

• chr13-30463308-T-C
• rs983723
• NM_002128.7:c.195A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002128.7(HMGB1):​c.195A>G​(p.Lys65Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,609,224 control chromosomes in the GnomAD database, including 2,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.074 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (1174 hom.)
• Consequence: HMGB1 NM_002128.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.604
• Publications: 5 publications found

Genes affected

HMGB1 (HGNC:4983): (high mobility group box 1) This gene encodes a protein that belongs to the High Mobility Group-box superfamily. The encoded non-histone, nuclear DNA-binding protein regulates transcription, and is involved in organization of DNA. This protein plays a role in several cellular processes, including inflammation, cell differentiation and tumor cell migration. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2015]

HMGB1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000285840 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 13-30463308-T-C is Benign according to our data. Variant chr13-30463308-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056340.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.604 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002128.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.195A>G	p.Lys65Lys	synonymous	Exon 3 of 5	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.195A>G	p.Lys65Lys	synonymous	Exon 3 of 5	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.195A>G	p.Lys65Lys	synonymous	Exon 3 of 5	NP_001300822.1	P09429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.195A>G	p.Lys65Lys	synonymous	Exon 3 of 5	ENSP00000345347.5	P09429
	HMGB1	ENST00000399489.5	TSL:1	c.195A>G	p.Lys65Lys	synonymous	Exon 2 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000927783.1		c.195A>G	p.Lys65Lys	synonymous	Exon 3 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11172 AN: 152194 Hom.: 1344 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0501

GnomAD2 exomes AF: 0.0193 AC: 4785 AN: 248390 AF XY: 0.0146

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.00659

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000947

Gnomad OTH exome AF: 0.00956

GnomAD4 exome AF: 0.00768 AC: 11193 AN: 1456912 Hom.: 1174 Cov.: 30 AF XY: 0.00662 AC XY: 4799 AN XY: 724756

African (AFR) AF: 0.260 AC: 8577 AN: 32932

American (AMR) AF: 0.0155 AC: 679 AN: 43690

Ashkenazi Jewish (ASJ) AF: 0.00621 AC: 162 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000798 AC: 68 AN: 85220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.0125 AC: 59 AN: 4734

European-Non Finnish (NFE) AF: 0.000555 AC: 617 AN: 1111080

Other (OTH) AF: 0.0172 AC: 1031 AN: 60106

GnomAD4 genome AF: 0.0735 AC: 11198 AN: 152312 Hom.: 1346 Cov.: 33 AF XY: 0.0709 AC XY: 5282 AN XY: 74496

African (AFR) AF: 0.254 AC: 10544 AN: 41518

American (AMR) AF: 0.0284 AC: 435 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68042

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0336 Hom.: 234

Bravo AF: 0.0832

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00130

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HMGB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs983723; hg19: chr13-31037445; COSMIC: COSV58105654; COSMIC: COSV58105654;